Supplementary Table S4: Loss of oncogenic B-Raf signaling induces transcripts associated with intestinal differentiation. Description of genes linked to intestinal differentiation and listed in Figure 5B. Depending on the differential regulation over time, genes might appear in only one cell line heat-map as only the top 50 hits is shown for each cell line. However, if a significant change in expression between DMSO and PLX4720 treated samples was detected, the gene is listed for the other cell line as well (see Supplementary Table S2). The arrows mark the mean direction of regulation over the time course. The abundance of transcripts at the individual experimental time points is shown in Supplementary Fig. S8.
Gene name / Cell line / Description / Ref.GSTA1 / Colo-205 ,
HT29 / Glutathione-S transferase; increased expression was reported for differentiation Caco-2 cells / (1, 2)
AKR1B10 / Colo-205
HT29 / Aldo-keto-reductase; highly expressed in small intestine and colon under physiological circumstances / (3)
HPGD / Colo-205 ¯,
HT29 / Prostaglandine catabolism acting in antagonistic fashion to COX2; Negatively regulated by b-Catenin in colorectal cancer cell lines; Highly expressed in differentiated murine and human intestinal cells; Loss-of-expression in human colon cancer; Tumor suppressor in the APCMin mouse model; Deletion of the murine Hpgd gene confers celecoxib resistance; Potential Cdx-2 target gene / (4-8)
KRT13 / HT29 / Keratin; upregulated during vitamin D induced differentiation of KRAS-mutant SW480 colon cancer cells / (9)
MAOA / Colo-205 / Mono-amin-oxidase, upregulated during vitamin D induced differentiation of KRAS-mutant SW480 colon cancer cells / (9)
RARRES1 / Colo-205 ,
HT29 / Highly expressed in terminally differentiated colorectal mucosa; Downregulation of RARRES1 is related to stage D progression; Implicated as tumor suppressor in various entities / (10, 11)
CLDN1 / Colo-205 ,
HT29 / Claudin-1; tight junction component; see main text for details
CLDN15 / Colo-205 / Claudin-15; tight junction component; see main text for details
CLDN18 / Colo-205 / Claudin-18; tight junction component; see main text for details
CES1 / Colo-205 / Carboxylesterase 1; Potential Cdx-2 target gene / (2, 12)
NRARP / Colo-205 / Notch1 target gene product with ankyrin repeats and negative feedback regulator of this pathway; Expression of NRARP in murine intestinal tissues, tumors and human CRC cell lines is positively correlated with expression of Cdx-1 and Cdx-2 / (13)
AMACR / Colo-205 ,
HT29 / a-Methylacyl-CoA racemase involved in β-oxidation of branched fatty and bile acids; In normal colonic mucosa, expression is restricted to the surface epithelium directly contacting the intestinal lumen; Expression is high in well to moderately differentiated but not in anaplastic CRCs; Potential Cdx-2 target gene; Loss of AMACR expression more frequently observed in proximal than distal CRCs; Lack of staining or low-intensity staining correlated with poor differentiation status, mucinous histology, lympho-vascular invasion and microsatellite instability / (12, 14-16)
UGT2B17 / Colo-205 / UDP-glucuronosyltransferase, highly upregulated in differentiating Caco-2 cells / (17)
MYO1A / Colo-205 ,
HT29 / Myosin expressed in the apical brush border of enterocytes; Frequently mutated or silenced in CRC; Acts as tumor suppressor upon ectopic expression in human CRC lines / (18, 19)
VAV3 / Colo-205 / RhoGEFs regulating cytoskeletal dynamics; Vav3 is predominantly expressed in apical regions of murine terminally differentiating cecal and colonic enterocytes / (20)
PVRL3 / HT29 / Cell adhesion molecule of the nectin family localized to adherens junctions; Increased expression was reported for differentiation in Caco-2 cells / (19)
NDRG1 / Colo-205 ¯,
HT29 / Upregulated during colonic differentiation; ectopic expression in human CRC lines induces hallmarks of differentiation and suppresses their invasive and metastatic potential / (21, 22)
TFF3 / Colo-205 ,
HT29 / Cdx-2 target gene and goblet cell differentiation marker; Component of intestinal mucus. / (23, 24)
PROM1 / Colo-205 ,
HT29 / Discussed as a marker of cancer stem cells in a variety of tumor entities; In normal colon tissue, however, Prominin1 is primarily expressed on the membrane of well-differentiated, Cdx-2-positive cells of the surface epithelium / (25)
TXNIP / Colo-205 ,
HT29 / Thioredoxin-interacting protein; Highly upregulated in differentiated colonic epithelium / (26)
HMGCS2 / Colo-205 ,
HT29 / Expression of 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) increases during differentiation of Caco-2 cells; Suppressed by Myc; Lost in poorly differentiated CRC; Responsive to histone deacetylase inhibitors / (27)
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